Extracellular cyclic ADP-ribose potentiates ACh-induced contraction in bovine tracheal smooth muscle

Luisa Franco, Santina Bruzzone, Pinfang Song, Lucrezia Guida, Elena Zocchi, Timothy F. Walseth, Emanuele Crimi, Cesare Usai, Antonio De Flora, Vito Brusasco

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41 Scopus citations


Cyclic ADP-ribose (cADPR), a universal calcium releaser, is generated from NAD+ by an ADP-ribosyl cyclase and is degraded to ADP-ribose by a cADPR hydrolase. In mammals, both activities are expressed as ectoenzymes by the transmembrane glycoprotein CD38. CD38 was identified in both epithelial cells and smooth myocytes isolated from bovine trachea. Intact tracheal smooth myocytes (TSMs) responded to extracellular cADPR (100 μM) with an increase in intracellular calcium concentration ([Ca2+]i) both at baseline and after acetylcholine (ACh) stimulation. The nonhydrolyzable analog 3-deaza-cADPR (10 nM) elicited the same effects as cADPR, whereas the cADPR antagonist 8-NH2-cADPR (10 μM) inhibited both basal and ACh-stimulated [Ca2+]i levels. Extracellular cADPR or 3-deaza-cADPR caused a significant increase of ACh-induced contraction in tracheal smooth muscle strips, whereas 8-NH2-cADPR decreased it. Tracheal mucosa strips, by releasing NAD+, enhanced [Ca2+]i in isolated TSMs, and this increase was abrogated by either NAD+-ase or 8-NH2-cADPR. These data suggest the existence of a paracrine mechanism whereby mucosa-released extracellular NAD+ plays a hormonelike function and cADPR behaves as second messenger regulating calcium-related contractility in TSMs.

Original languageEnglish (US)
Pages (from-to)L98-L106
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number1 24-1
StatePublished - Jan 2001
Externally publishedYes


  • Acetylcholine
  • Adenosine 5′-diphosphate-ribosyl cyclase
  • CD38
  • Calcium-related contraction of tracheal strips
  • Cyclic adenosine 5′-diphosphate-ribose hydrolase
  • Nicotinamide adenine dinucleotide/cyclic adenosine 5′-diphosphate-ribose-mediated paracrine mechanisms


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